Electrocardiogram reconstruction from implanted device electrograms

ABSTRACT

A method of reconstruction of the standard 12-lead surface EKG given values of the electrical potential from an implanted medical device is described. This implanted device can be oriented in an arbitrary fashion and reconstruction technique is obtained through physical measurement of the orientation of the implanted device or correlation with a standard 12-lead EKG obtained from the patient.

This is a divisional application that claims priority to U.S. patentapplication Ser. No. 12/233,297 (now issued as U.S. Pat. No. 8,200,318),filed on Sep. 18, 2008, which claims priority to U.S. provisional patentapplication Ser. No. 60/994,682, filed Sep. 21, 2007, each of which isherein incorporated by reference in its entirety.

FIELD OF INVENTION

The present invention is related to the field of cardiology. In oneembodiment, the present invention contemplates generating areconstructed electrocardiogram (rEKG) free of extraneous electricalactivity. For example, an implanted device detects intracardiacelectromyograms (EMG's) that are compared with a traditional surface EKGpattern (i.e., for example, a 12-lead surface EKG; sEKG) to calculateEMG/sEKG correlation parameters. The EMG/sEKG correlation parameters arethen used to transform the EMG vectors into an rEKG. Such rEKGs areuseful for diagnostic and therapeutic purposes. The implanted device maybe a sensor device, a pacemaker and/or a defibrillator.

BACKGROUND OF THE INVENTION

Implanted devices are well suited for recording intracardiac electricalpotentials (i.e., for example, electromyograms; EMG) because they areisolated from electrical signals from outside the body. The morphologyof an EMG reflects local and global electrical activity of the heart.There has been a dramatic increase in the utilization of implantablecardioverter defibrillators (ICD's) and pacemakers and as a result,there is an abundance of EMG information available. However, fewattempts have been made to extract information from the EMG's aside fromthe discrimination of supraventricular (SVT) and ventriculartachycardias (VT). One reason that these attempts have not beensuccessful is due to the fact that the unknown and arbitrary orientationof the recording device prevents rapid interpretation by medicalpersonnel.

What is needed is an electrocardiogram reconstruction technique usingelectrical potentials obtained from a device implanted within a patient.

SUMMARY

The present invention is related to the field of cardiology. In oneembodiment, the present invention contemplates generating areconstructed electrocardiogram (rEKG) free of extraneous electricalactivity. For example, an implanted device detects intracardiac EMG'sthat are compared with a traditional surface EKG pattern (i.e., forexample, a 12-lead surface EKG; sEKG) to calculate EMG/sEKG correlationparameters. The EMG/sEKG correlation parameters are then used totransform the EMG vectors into an rEKG. Such rEKGs are useful fordiagnostic and therapeutic purposes. The implanted device may be asensor device, a pacemaker and/or a defibrillator.

In one embodiment, the present invention contemplates a method,comprising: a) providing: i) a traditional electrocardiogram (sEKG)derived from skin surface electrodes; ii) at least one intracardiacelectromyogram (EMG) derived from an implanted cardiac device, whereinsaid device is connected a plurality of electrode leads; b) comparingsaid sEKG and said EMG to obtain an EMG/sEKG correlation parameter; andc) calculating a reconstructed electrocardiogram using said correlationparameter and said EMG. In one embodiment, the electrode leads areselected from the group comprising right-sided leads or left-sidedleads. In one embodiment, the leads are selected from the groupcomprising extended V-leads or extended A-leads. In one embodiment, thesEKG is collected at the same time as said EMG. In one embodiment, thesEKG is collected at a different time as said EMG. In one embodiment,the skin surface electrodes are in known positions. In one embodiment,the device electrode leads are in known positions. In one embodiment,the known positions are determined by a technique selected from thegroup consisting of radiography, ultrasonography, computerized acoustictomography, and magnetic imaging resonance, or other imaging techniques,including but not limited to, impedance localization, or magneticmapping techniques

In one embodiment, the present invention contemplates a system,comprising: a) an implanted cardiac device comprising a positionalsensor, wherein said device is connected to a plurality of electrodeleads, and wherein said leads provide intracardiac electromyograms(EMG); b) a computer comprising at least one microprocessor, whereinsaid computer is operably linked to said cardiac device; c) a pluralityof EMG/sEKG correlation parameters residing on said at least onemicroprocessor, wherein each parameter is derived from differentialdata, from said positional sensor; and d) an algorithm residing on saidat least one microprocessor, wherein said algorithm calculates areconstructed EKG (rEKG) using said EMG and said correlation parametersor is calculated through an orthogonal vectorcardiogram (VCG) as anintermediate. In one embodiment, the rEKG is calculated on-demand. Inone embodiment, the rEKG is calculated automatically and continuously.In one embodiment, the automatic calculation is performed in response toalterations in said EMG. In one embodiment, the automatic calculation isperformed in response to alterations in said positional sensor data. Inone embodiment, the at least one microprocessor further comprises aplurality of rEKG threshold exceedances. In one embodiment, the rEKGthreshold exceedance provides a warning signal. In one embodiment, therEKG threshold exceedance provides a preliminary diagnosis. In oneembodiment, the method further comprises a transmission device capableof sending data selected from the group consisting of EMG, EMG/sEKGcorrelation parameters, positional data, and rEKG to a remote location.

A method, comprising: a) providing: i) a subject exhibiting symptoms ofa cardiac disease; ii) a system capable of calculating a reconstructedelectrocardiogram (rEKG) specific for said subject; iii) a testingparameter known to detect said cardiac disease; b) administering saidtesting parameter to said subject under conditions such that said rEKGdetects said cardiac disease. In one embodiment, the detected cardiacdisease comprises ischemia. In one embodiment, the method detectscardiac structural diseases, including but not limited to, cardiacmuscle diseases (i.e., for example, pericarditis, myocarditis, etc.). Inone embodiment, the method detects pulmonary diseases (i.e., forexample, pulmonary embolism, pulmonary hypertension, chronic obstructivepulmonary disease, etc.). In one embodiment, the method detects centralnervous system disorders (i.e., for example, stroke, cranial bleeding,etc.). In one embodiment, the method detects cardiac conduction systemdiseases (i.e., for example, sick sinus syndrome, atrioventricular nodalblock of degrees 1, 2 and 3, etc.) In one embodiment, the detectedcardiac disease comprises electrolyte abnormalities. In one embodiment,the detected cardiac disease comprises a myocardial infarction. In oneembodiment, the detected cardiac disease comprises heart rhythmdiscrimination. In one embodiment, the testing parameter comprises atleast one medication. In one embodiment, the testing parameter comprisesa stress test. In one embodiment, the testing parameter comprises a saltcomplex.

Definitions

The term “traditional electrocardiogram” or “standard electrocardiogram”as used herein is abbreviated as “sEKG” and refers to a heart rhythmtracing generated by collecting electrical signals from skin surfaceelectrodes. These sEKGs comprise the P-Q-R-S-T heart waveform complexuseful in diagnosing a variety of cardiac diseases.

The term “skin surface electrodes” as used herein refers to anyelectrically conductive material placed upon the skin surface capable oftransmitting electrical potential information. A properly placed arrayof skin surface electrodes connected to a conventionalelectrocardiograph device can result in the production of an sEKG.

The term “intracardiac electromyogram” as used herein is abbreviated as“EMG” and refers to a cardiac muscle contractility tracing generated bycollecting electrical signals from electrode leads placed in specificheart locations. These EMGs comprise relative contraction/relaxationrates for each heart location useful in diagnosing a variety of cardiacdisorders.

The term “electrode leads” as used herein refer to any electricallyconductive material placed on the exterior or interior surface of aheart muscle (i.e., for example, ventricular muscle and/or atrialmuscle) capable of transmitting electrical potential information. Aproperly placed array of electrode leads connected to an implantedcardiac device (i.e., for example, a defibrillator and/or a pacemaker)can result in the production of an EMG.

The term “EMG/sEKG correlation parameter” as used herein refers to aproduct of an algorithm comprising EMG and sEKG data calculations. Thisalgorithm may vary depending upon the relative positioning of the heartwithin the chest cavity of the same subject (i.e., for example, anEMG/sEKG correlation parameter taken in the supine position will differfrom an EMG/sEKG correlation parameter taken in the standing position).Consequently, the correlation parameter may be used to correct for anunknown electrode lead position in order to provide an rEKG.

The term “reconstructed electrocardiogram” as used herein is abbreviatedas “rEKG” and refers to the generation of a conventional P-Q-R-S-T heartwaveform pattern by utilizing an algorithm based upon an EMG/sEKGcorrelation parameter and EMG data.

The term “implanted cardiac device” as used herein refers to any devicecapable of providing functional heart data. For example, such a devicemay comprise a pacemaker, a defibrillator or other sensor device.Further, these devices may also comprise a positional sensor that iscalibrated to detect gravitational forces such that the anatomicalpositioning of the heart may be determined. Such devices may behardwired, or preferably are wireless, to support data communicationwith remote data collection devices (i.e., for example, a desktopcomputer and/or laptop computer). An implanted cardiac device isoperably connected to a plurality of electrode leads capable of two-wayelectrical signal transmission. For example, electrode leads mayinclude, but are not limited to, right-sided leads (contacting the rightside of the heart), left-sided leads (contacting the left side of theheart), extended V-leads (contacting the ventricle) and/or extendedA-leads (contacting the atria).

As used herein, the term “atria” refers to the upper principal cavity ofthe heart auricle (i.e., the sinus venosus) and is situated posteriorlyto the smaller cavity of the auricle, the appendix auricula. The humanheart comprises two atria, one on the left side of the heart and asecond on the right side of the heart. Consequently, the term “atrial”references any matter of, or concerning, either one or both atria.

As used herein, the term “ventricle” refers to the lower, and largest,compartment of the heart. The human heart comprises two ventricles, oneon the left side of the heart and a second on the right side of theheart. Consequently, the term “ventricular” references any matter of, orconcerning, either one or both ventricles.

The term “at the same time” as used herein refers to the collection ofdifferent data sets in near real-time. While not necessarilysimultaneously, it is preferred that such data sets are collected within5-100 msec, preferably within 25-75 msec, and most preferably within30-50 msec of each other.

The term “at different times” as used herein refers to the collection ofdifferent data sets separated in time. For example, such timeseparations may include, but are not limited to, minutes, hours, daysand/or years.

The term “computer” as used herein refers to any device capable ofperforming serial and/or parallel mathematical calculations utilizing analgorithm (i.e., for example, a software program) that resides withinthe device. Generally, such algorithms reside on a plurality ofmicroprocessors that are in electrical communication with the computer,wherein the microprocessors can receive, store, and transmit data.

As used herein, the term “microprocessor” refers to a programmabledigital electronic component that incorporates the functions of acentral processing unit on a single semi-conducting integrated circuit.

As used herein, the term “storage memory” refers to any electronic meansthat is capable of retaining digitized information or computer softwareprograms. The digitized information may be binary or complex formulas orequations capable of receiving, and processing, input from atrial orventricular sensing leads.

The term “differential data” as used herein refers to the comparison oftwo or more data sets describing the same endpoint but under dissimilarenvironmental conditions. For example, the calculation of an EMG/sEKGcorrelation parameter when a subject is supine, represents differentialdata when compared to the calculation of an EMG/sEKG correlationparameter with the same subject is standing.

The term “on-demand” as used herein refers to an instruction to performan rEKG calculation a single time. Such an instruction is generallyprovided by a medical technician, doctor, and/or patient in response toan unexpected medical condition, or as part of an expected testingprotocol.

The term “automatically” as used herein refers to an instruction toperform an rEKG calculation whenever specific, pre-identified,conditions exist. Such conditions may be part of an algorithm residingon a computer microprocessor that trigger the calculation of an rEKG.The series of rEKGs are then placed in memory storage for laterretrieval.

The term “threshold exceedances” as used herein refers to any presetlimit for a physiological condition reflected by an rEKG value.Generally, when such preset limits are exceeded a subject's medicalcondition has been significantly altered that may, or may not, requiremedical attention. For example, a threshold exceedance may signal awarning that medication administration is overdue. Alternatively, athreshold exceedance may provide sufficient information such thatmedical personnel can establish a preliminary diagnosis for a suspectedcardiac disease.

The term “symptom” as used herein refers to any alteration of ameasurable biological response (i.e., for example, respiration, heartrate, blood cell count, hormone levels etc.) that are outside normallimits as generally accepted by the medical profession.

The term “cardiac disease” as used herein refers to any alteration ofheart function based upon parameters including, but not limited to,electrical and/or muscular balance. Specific cardiac diseases mayinclude, but are not limited to, myocardial infarction, ischemiccardiomyopathy, angina pectoris, heart rhythm arrhythmias, tachycardias,congestive heart failure, and/or atrial fibrillation, nerve conductiondisorders, thrombophilia, atherosclerosis, hypertension,arteriosclerosis, cardiomyopathy, hypertension, and/or arterial orvenous stenosis, or valvular heart disease

“Symptoms of cardiac disease” as used herein refers to any clinicalmanifestation of a disease state associated with the heart and thecentral or peripheral arterial and venous vasculature. For example, saidclinical manifestations include, but are not limited to pain, weakness,high blood pressure, elevated plasma cholesterol, elevated plasma fattyacids, tachycardia, bradycardia, abnormal electrocardiogram, external orinternal bleeding, headache, dizziness, nausea and vomiting. Thus, apatient suffering from, or exhibiting symptoms of, cardiovasculardisease may detect certain symptoms (i.e., pain), while other symptomsmay not be noticeable to the patient, but are detectable by a healthcare provider (i.e., elevated blood pressure).

As used herein, the term “patient” or “subject” refers to a human ornon-human organism that is either symptomatic or asymptomatic forcardiovascular disease. Preferably, a human patient is under thesupervision of a physician or hospitalized.

As used herein the phrase, “patients at risk for cardiac disease” referto patients who have an increased probability, as compared to thegeneral population, of developing some form of cardiac disease in theirlifetime. Patients at risk for cardiac disease generally have one ormore risk factors for cardiac disease. Risk factors for cardiac diseaseinclude, but are not limited to, a history of smoking, a sedentarylifestyle, a family history of cardiovascular disease, lipid metabolicdisorders, diabetes mellitus and obesity.

The term “testing parameter” as used herein refers to any substance oractivity that modifies heart function such that an underlying cardiacdisease may be detected. For example, the administration of a medicationmay detect angina and/or ischemia (i.e., for example, nitroglycerin).Alternatively, administering a subject to a treadmill stress test maydetect a risk for myocardial infarction. Further, administering asubject a salt complex (i.e., for example, a mixture of sodium chlorideand potassium chloride) may detect electrolyte imbalances.

As used herein, the term “system” refers to any integrated singledevice, or multiple devices connected together, that function in acoordinated manner to produce a desired result. One example illustratedherein, describes a system that calculates an rEKG in real-time with thecollection of EMG data.

As used herein, the term “algorithm” refers to a precise list of precisesteps, and/or a finite list of well-defined instructions, foraccomplishing some task that, given an initial state, will terminate ina defined end-state.

The term “augmented vector right” or “AvR” as used herein, refers to anyelectrode lead having a positive electrode on the right arm. Thenegative electrode comprises a combination of the left arm electrode andthe left leg electrode, which “augments” the signal strength of thepositive electrode on the right arm. The “AvR” represents one (1) of thestandard twelve (12) projections of the 12-lead EKG.

The term “augmented vector left” or “AvL” as used herein, refers to anyelectrode lead having a positive electrode on the left arm. The negativeelectrode comprises a combination of the right arm electrode and theleft leg electrode, which “augments” the signal strength of the positiveelectrode on the left arm. The “AvL” represents one (1) of the standardtwelve (12) projections of the 12-lead EKG.

The term “augmented vector foot” or “AvF” as used herein, refers to anyelectrode lead having a positive electrode on the left leg. The negativeelectrode is a combination of the right arm electrode and the left armelectrode, which “augments” the signal of the positive electrode on theleft leg. The “AvF” represents one (1) of the standard twelve (12)projections of the 12-lead EKG.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 depicts a cutaway drawing of an exemplary human heart showing theconfiguration of one embodiment of dual chamber implantable cardiacpacer/defibrillator.

FIG. 2 shows an exemplary normal sinus rhythm tracing in a mouse.

FIG. 3 presents an exemplary data comparison of a pig rEKG tracing takenfrom Lead I of an implanted defibrillator with its paired sEKG tracing.

FIG. 4 presents an exemplary data comparison of a pig rEKG tracing takenfrom Lead III of an implanted defibrillator with its paired sEKGtracing.

FIG. 5 presents an exemplary data comparison of a pig rEKG tracing takenfrom Lead V1 of an implanted defibrillator with its paired sEKG tracing.

FIG. 6 depicts the superimposed tracings of recorded (blue) andreconstructed (red) EKG tracings obtained from three EKG projections(AvR, AvL and AvF) in human patients implanted with a defibrillator.Each EKG reconstruction represents 700 matrix relationships.

FIG. 7 depicts the superimposed tracings of recorded (blue) andreconstructed (red) EKG tracings obtained from three EKG projections(AvR, AvL and AvF) in human patients implanted with a defibrillator.Each EKG reconstruction represents 100 matrix correlations.

DETAILED DESCRIPTION

The present invention is related to the field of cardiology. In oneembodiment, the present invention contemplates generating areconstructed electrocardiogram (rEKG) free of extraneous electricalactivity. For example, an implanted device detects intracardiacelectrograms (EMG's) that are compared with a traditional surface EKGpattern (i.e., for example, a 12-lead surface EKG; sEKG) to calculateEMG/sEKG correlation parameters. The EMG/sEKG correlation parameters arethen used to transform the EMG vectors into an rEKG. Such rEKGs areuseful for diagnostic and therapeutic purposes. The implanted device maybe a sensor device, a pacemaker and/or a defibrillator.

I. Heart Function

The operation of the heart is regulated by electrical signals producedby the heart's sinoatrial (SA) node. Each signal produced by the SA nodespreads across the atria and ventricles of the heart, depolarizing themuscle fibers as it spreads. Atrial and ventricular contractions occuras the signal passes. After contracting, the myocardial cells repolarizeduring a short period of time, returning to their resting state. Oncerepolarized, the muscle cells are ready to be depolarized again by asignal from the SA node.

At rest, the normal adult SA node produces a signal approximately 60 to85 times a minute, causing the heart muscle to contract, and therebypumping blood to the remainder of the body. This constitutes therepetitive, cyclic behavior of the heart. Each cycle in the operation ofthe heart is called a cardiac cycle.

Atrial geometry, atrial anisotropy, and histopathologic changes in theleft or right atria can, alone or together, form anatomical obstacles.The obstacles can disrupt the normally uniform propagation of electricalimpulses in the atria. These anatomical obstacles (called “conductionblocks”) can cause the electrical impulse to degenerate into severalcircular wavelets that circulate about the obstacles. These wavelets,called “reentry circuits,” disrupt the normally uniform activation ofthe left and right atria. Abnormal, irregular heart rhythm calledarrhythmia, results. This form of arrhythmia is called atrialfibrillation, which is a very prevalent form of arrhythmia.

To analyze the heart's operation, a variety of techniques have beendeveloped for collecting and interpreting data concerning the electricalactivity of the heart. One of the most basic of these approaches is theelectrocardiogram (EKG). As an electrical signal spreads across theheart, an EKG repetitively measures the voltages at various electrodesrelative to a designated “ground” electrode. The EKG typically plotseach lead over an interval of time such that the heart's electricalactivity for one or more cardiac cycles is displayed for purposes ofmonitoring or analysis. The three most common EKG's are known as the “12lead”, the “18 lead,” and the vector cardiograph.

A cardiac cycle as measured by the EKG is partitioned into three mainelements, which reflect the electrical and mechanical operation of theheart. The portion of a cardiac cycle representing atrial depolarizationis referred to as a “P-wave.” Depolarization of the ventricular musclefibers is represented by “Q”, “R”, and “S” points of a cardiac cycle.Collectively these “QRS” points are called an “R-wave” or a “QRScomplex.” The portion of a cardiac cycle representing repolarization ofthe ventricular muscle fibers is known as a “T-wave.” It is through theuse of an EKG that one is able to determine whether fibrillation is oris not occurring and allows one to manipulate the heart tissue toprovide treatment.

II. Pacemakers

A pacemaker maintains the heart rate of a patient between a certainprogrammable range. For example, in humans that range is typicallybetween 60 to 80 beats per minute (lower rate) and 120 to 160 beats perminute (upper rate). In one embodiment, the present inventioncontemplates a pacemaker for stimulating the independent conductionzones and reestablishing functional communication between the zones. Apacemaker automatically applies a pacing impulse to the heart ofsufficient magnitude to depolarize the tissue. The device is adapted tocontinue delivering intermittent pacing to the heart in the event thatthe heart fails to return to its normal behavioral pattern, and has theability of automatically regaining sensing control over a functionalheart, thereby insuring that further pacing is inhibited.

The pacemaker circuit comprises two basic subsystems; a sensing system,which continuously monitors heart activity; and a stimulation systemwhich upon receiving a signal from the sensing system applies a pacingimpulse to the myocardium through an intravascular electrical lead. Afirst bipolar lead may be coupled to the pulse generator and has anelectrode located at its distal end to sense and pace the atrium.Alternatively, the atrial leads may comprise separate sensing and pacingelectrodes. A second bipolar lead coupled to the generator is used forsensing and pacing the ventricle. Alternatively, the ventricular leadsmay comprise separate sensing and pacing electrodes. A circuit isprovided for applying impedance measuring current pulses between one ofthese electrodes and the others.

A. Sensing Elements of a Pacemaker

In a standard dual chambered pacemaker, the sensing circuits monitoractivity both in the atrium and ventricle. If a sensed event occurs inthe atrium, this initiates a ventricular paced event if no ventricularactivity occurs during the programmed atrio-ventricular delay. If nosensing occurs in the atrium or ventricle, pacing is initiated tomaintain the programmed lower rate.

When the pacemaker device is used for the present invention, similarsensing algorithms will be useful in the appropriate pacing of thevarious intracardiac segments. It is particularly desirable that thepacemaker include a sensor of a physiologic parameter related to demandfor cardiac output, such as an activity sensor, a respiration sensor oran oxygen saturation sensor. Various dual chamber pacing devices haveincorporated some form of sensor to provide a physiologic pacing rate.Similar sensing is contemplated for the present invention to maintain aphysiologic rate.

B. Pacing Elements

In a standard dual chamber pacemaker, pacing of both atrium andventricle is possible. In the current invention, pacing of the variouselements will take place once requested by the sensing algorithm. Thestandard burst generator pacemaker employs appropriate technology forthe generation of stimulation pulses in the form of individual pulses orpulse trains having an amplitude up to 7 V and a pulse width of up to 1msec. Most pacemakers have these parameters as a programmable option.The pacing rate is also programmable in most pacemakers and the range isbetween 35 to 160 beats/min.

Given that the circuitry for pulse generation has become well known tothose skilled in the art, no detailed disclosure is included herein.Specific timing, amplitude, duration and the number of pulses iscontrolled by a microprocessor via data bus under the control of aprogram stored in memory.

III. Implantable Cardiac Defibrillators

Implantable cardiac defibrillators (ICDs) have significantly reduced therisk of sudden death following hospital discharge, but arrhythmia riskand associated mortality remains an important problem. Buxton et al.,Current Approaches To Evaluation And Management Of Patients WithVentricular Arrhythmias, Med Health R I, 84(2):58-62 (2001) Arrhythmiasare known to occur in patients having congestive heart failure, atrialfibrillation, ventricular tachyarrhythmias, and bradyarrhythmias. Atrialfibrillation, in particular, is treatable with rate controlanticoagulation or cardioversion followed by maintenance of sinusrhythm. In patients surviving malignant ventricular arrhythmias,however, implanted cardiac defibrillators are especially beneficial.Specifically, in patients with coronary artery disease, decreasedejection fraction, with or without nonsustained ventricular tachycardia,defibrillator implantation can improve survival. Lampert et al.,Management Of Arrhythmias, Clin Geriatr Med, 16(3):593-618 (2000)

Identifying the mechanism of an arrhythmia based on intracardiacelectrograms has become a challenge in the clinical use of implantablecardiac defibrillators. Implantable cardiac defibrillators are primarilydesigned to deliver therapy for life-threatening ventricular arrhythmiasbut frequently deliver inappropriate shocks during supraventriculartachycardias. Tanaka S., An Overview Of Fifth-Generation ImplantableCardioverter Defibrillator, Ann Thorac Cardiovasc Surg., 4:303-311(1998); Thompson et al., supra; Gold et al., A New DefibrillatorDiscrimination Algorithm Utilizing Electrogram Morphology Analysis,Pacing Clin Electrophysiol. 1999; 22:179-182 (1999); Barold et al.,Prospective Evaluation Of New And Old Criteria To Discriminate BetweenSupraventricular And Ventricular Tachycardia In ImplantableDefibrillators, Pacing Clin Electrophysiol., 21:1347-1355 (1998); andSchaumann et al., Enhanced Detection Criteria In ImplantableCardioverter-Defibrillator To Avoid Inappropriate Therapy, Am J.Cardiol., 78:42-50 (1996)

In one embodiment, the present invention contemplates an implantablecardiac defibrillator 13 attached to pacemaker 14. See, FIG. 1. It isnot intended that the scope of the present invention by limited by theherein exemplary device. In fact, many possible engineering designs arecompatible with the embodiments described herein.

The pacemaker/defibrillator is implanted in a surgically-formed pocketin the flesh of the patient's chest 10, or other desired location of thebody. Signal generator 14 is conventional and incorporates electroniccomponents for performing signal analysis and processing, waveformgeneration, data storage, control and other functions, power supply 40(battery or battery pack), which are housed in a metal case (can) 15compatible with the tissue and fluids of the body (i.e., biocompatible).The device is microprocessor-based with substantial memory, logic andother components to provide the processing, evaluation and otherfunctions necessary to determine, select and deliver appropriate therapyincluding electrical defibrillation and pulses of different energylevels and timing for ventricular defibrillation, cardioversion, andpacing to the patient's heart 16 in response to ventricular arrhythmiaand supraventricular tachycardia.

Composite electrical lead 18 which includes separate leads 22 and 27with distally located electrodes is coupled at the proximal end tosignal generator 14 through an electrical connector 20 in the header ofcase 15. Preferably, case 15 is also employed as an electrode such aselectrical ground, for unipolar sensing, pacing or defibrillation.Unlike the defibrillator devices used in previous methods, the signalgenerator and lead(s) of the present invention may be implemented foratrial and ventricular sensing, pacing and defibrillation.Defibrillating shocks of appropriate energy level may be applied betweenthe case and electrode 21 on lead 22 implanted in the right atrium 24through the superior vena cava 31, or between the case and electrode 26on lead 27 implanted through the superior vena cava in the rightventricle 29. Leads 22 and 27 and their associated distal tip electrode32 (to a separate conductor) and distal tip electrode 35 (also to aseparate conductor within the lead), respectively, may be used for botha sensing lead and a pacing lead in conjunction with the circuitry ofsignal generator 14. One of skill in the art may easily recognize thatseparate sensing and pacing leads are also compatible with thisdescribed system. To that end, electrode 32 is positioned in the rightatrium against either the lateral or anterior atrial wall thereof, andelectrode 35 is positioned in the right ventricle at the apex thereof.

Active or passive fixation of the electrodes may be used to assuresuitable excitation. Tip electrode tip 35 preferably has a standard 4 to8 millimeter (mm) configuration, and is provided with soft barbs (tines)to stabilize its position in the ventricle. Each of the electrodes,those used for defibrillation and cardioversion, as well as those usedfor sensing and for pacing, are electrically connected to separateconductors in leads 22 and 27.

If desired, rather than simply using metal case 15 as an electrode, aconductive pouch 37 comprised of a braided multiplicity of carbon fine,individual, predominantly isotropic wires such as described in U.S. Pat.No. 5,143,089 (herein incorporated by reference) is configured toreceive, partly enclose and maintain firm electrical contact with thecase. This serves to enhance the effectiveness of the anodal electrodeof the case and establish a better vector for the electric fieldproduced by the defibrillation shock waveform, and thereby lower thedefibrillation threshold. The conductive pouch can be electricallyconnected directly to an extension lead 38 composed of similar carbonbraid of about 7 french diameter which is implanted subcutaneously forconnection to an epicardial or pericardial patch electrode (not shown)or as a wire electrode (as shown) through an opening formed by puncturesurgery at 39. The conductor for electrode 36 of lead 38 may beimplanted subcutaneously to a point 39, and then by puncture surgerythrough the thoracic cage and the pericardial sac, under a localanesthetic. The lead 38 is run parallel to the sternum, through thepuncture, and then through the patient's thoracic cage and into thepericardial sac. It may even be threaded through the thoracic cage, thepericardial space about the left ventricle and atrium, and back alongthe right atrial appendage, external to the heart. The distal end 36 oflead 38 is preferably placed close to the left atrium of the patient'sheart to provide an increase in electric field strength and support thestrong vector of the electric field according to the heart chamber to bedefibrillated. Selection of the chamber (i.e., atrium or ventricle)which is to undergo defibrillation is made by choosing the appropriateendocardial counter-electrode (21 or 26, respectively) to be energizedtogether with the carbon electrode, if the case 15 or conductive pouch37 is not used directly as the other electrode.

Fabricating the electrode portion of conductor 38 (from the point ofentry 39 into the thoracic cage) of carbon braid provides the desirablefeatures described earlier herein. Proper intracardiac positioningimproves the vector for defibrillation through the atrium as well as theventricle.

Atrial coil electrode 21 is used for bipolar sensing as well as acounter-electrode for defibrillation. Hence, electrode 21 is preferablyalso composed of a braided carbon fiber material described in the '089patent, to take advantage of its very low polarization and lowdefibrillation threshold, to allow the intrinsic rhythm to be detectedalmost immediately after delivery of a shock for accurate determinationof the current status of electrical activity of the atrium. The featuresof low polarization and accurate sensing are important for detection andevaluation of atrial status since atrial signals have magnitudes of onlyabout 20% to 25% those of ventricular signals because of the smalleratrial mass. The braided carbon fiber structure of electrode 21 is alsodesirable to provide a large effective electrical surface area (forexample, in a range from three to six square centimeters) relative toits considerably smaller geometric area, which provides greater energyefficiency for defibrillation.

As with atrial electrode 21, ventricular electrode 26 of lead 27 ispositioned for use as a defibrillation electrode as well as for bipolarsensing in the ventricle. For defibrillation, electrode 26 alsocooperates with the metal case 15, pouch electrode 37, or pericardialelectrode 36, whichever of these latter electrodes is used in thedefibrillator implementation. Again, a braided conductive structure forelectrode 26 provides it with an effective surface area considerablylarger than its actual exposed surface area. As an alternative, theelectrode may be composed of fine metallic filaments and fibers ofplatinum iridium alloy, braided together to offer similarly desirableelectrode characteristics.

Thus, the tip electrodes of leads 22 and 27 are used for sensing andpacing of the respective atrial and ventricular chambers as in aconventional pacemaker, with dual-chamber pacing, dual-chamber sensing,and both triggered and inhibited response. Further, the defibrillator 13uses a transvenous electrode for ventricular defibrillation andstimulation and an atrial bipolar lead for sensing and atrialdefibrillation, so that atrial defibrillation is performed with one ofthe same electrodes used for atrial stimulation and sensing.

Rather than terminating at distal tip electrode 32, the latter electrodemay be positioned at mid-lead of the atrial transvenous lead 22 whichextends and is threaded through right atrium, ventricle, pulmonaryvalve, and into the left pulmonary artery, with a coil counter-electrode42 connected to a separate conductor of the lead. With this alternativeembodiment, a defibrillating waveform can be applied between electrode42 and atrial defibrillation electrode 21 upon detection of atrialfibrillation. In that configuration, electrode 42 would replace signalgenerator case 15, conductive pouch 37, or lead portion 36 as theselected electrode, and enables a strong vector for the electric fieldthrough right and left atrium. Rather than placement in the leftpulmonary artery, electrode 42 may be positioned in the distal coronarysinus for defibrillation of the atrium in conjunction with electrode 21.

Defibrillation of the atrium and ventricle is achieved by application ofdefibrillation waveforms of suitable shape and energy content betweenappropriate electrodes, such as electrode 36 and electrode 21 for atrialfibrillation, or between electrode 42 and electrode 21 for atrialfibrillation; or between electrode 36 and electrode 26 for ventricularfibrillation, in which atrial electrode 21 can be used additionally aseither anode or cathode. The case 15 can serve as the anode for deliveryof the shock as well, and can provide ground reference potential forunipolar sensing and pacing, in both chambers.

IV. Intracardiac EMG→EKG Construction

In one embodiment, the present invention contemplates a methodcomprising generating an rEKG pattern using intracardiac EMG vectors andEMG/sEKG correlation parameters. In one embodiment, the EMG vectors arecollected from patients implanted with devices including, but notlimited to, pacemakers, defibrillators, cardiac rhythm managementdevices, or any other device that provides intracardiac signals.Although it is not necessary to understand the mechanism of aninvention, it is believed that EKG reconstruction expands the use ofimplantable devices generally used for arrhythmia detection andtreatment, to overall cardiac diagnostics. Some advantages of using EKGreconstruction diagnostics instead of traditional EKG diagnostics isthat it provides real-time continuous monitoring, which can be used formultiple purposes including but not limited to: i) ischemia detection;ii) myocardial Infarction detection; iii) electrolyte abnormalitiesdetection; iv) assessment of effect of medications; or v) improvedrhythm discrimination.

Various methods have been reported that may detect intracardiacelectrical potential fields or cardiac electrogram recordings. U.S. Pat.No. 4,649,924. Further, methods have been reported for: i) automated EKGanalysis of heart rate (U.S. Pat. No. 5,738,104); ii) determination ofST segment deviation (U.S. Pat. Nos. 4,546,776 and 3,868,567); iii)providing real-time monitoring of heart function via external systems(U.S. Pat. No. 4,679,144); and iv) providing computer assistedmonitoring (U.S. Pat. No. 5,003,983). Methods for detecting changes inthe major deflection of the electrocardiogram QRS axis and axis shiftwith filtering of recordings from an implantable device have also beenreported. U.S. Pat. Nos. 6,324,421 & 6,397,100 (all of the above patentsare herein incorporated by reference). These previously reportedmethods, however, do not establish a method for converting arbitraryelectrical fields obtained inside the body or inside the heart from animplanted device into reconstructed surface electrocardiograms (i.e.,for example, an rEKG) that are interpretable for subsequent analysis.

A specific implementation of a reconstructed vectorcardiogram (VCG) froman implanted device has been described. See, U.S. Pat. No. 6,766,190.There are however, several differences between this technique and thosedescribed herein.

For example, the '190 patent describes forming a VCG from implanteddevice recordings, which are compared to the Frank method. In someembodiments of the present invention, a reconstructed VCG or EKGprovides an accurate reconstruction of surface EKGs thereby allowing forrapid interpretation by presently trained physicians. Further, the '190patent does not describe or provide any method for reconstructingsurface EKG tracings from measured VCGs.

The '190 patent also uses an external electrical pulse to adjust gainand determine the x-axis orientation of the VCG with regard to theexternally measured EKG. In some embodiments of the present invention,this is done via a correlation algorithm obtained from singlesimultaneous measurement of surface EKG with recordings from theimplanted device.

Algorithm methods described within the '190 patent provide that threeorthogonal constant current pulses are used to determine the axes of theimplanted device. In some embodiments of the present invention, noexternal electrical field or current generation is required to determinethe orientation or adjust the gain of the implanted device—this is doneby simultaneous recording from the device and surface of the heart's ownelectrical activity.

A technique using a matrix to convert voltage signals from an implanteddevice into a surface EKG has also been reported. Kroll et al., U.S.Pat. No. 6,980,850. The '850 patent describes a matrix conversion fromvectorcardiograph to electrocardiogram is described using a series ofweighting signals (step 352). These weighting factors are then adjustedby the device to form an emulated EKG. In some embodiments of thepresent invention, methods of forming a reliable surface EKG emulationare described using simultaneous recording of a surface EKG andintracardiac EKG. In one embodiment, an exact solution for thetransformation from implanted recording data is calculated via matrixinversion. Although it is not necessary to understand the mechanism ofan invention, it is believed that this process provides an exactorientation of the vectors that reconstruct the EKG, thereby supplying areproduction of the tracing that can be scaled simply by multiplying bya single constant. In another embodiment, a method reconstructs thesurface EKG by exhaustive search of all possible orientation of theprojection vector. Although it is not necessary to understand themechanism of an invention, it is believed that numerous scaling factorsare systematically used in an algorithm to find a “best fit” of thereconstructed vector and this scaling factor is then recorded forsubsequent reconstructions.

The '850 patent uses a series of weighing factors Km withoutdetermination of the axis of projection of the implanted electrogram.This is unlike the presently described embodiments wherein the relativelocation of the recorded vector can be determined, and thus thecontribution of change from various positions (sitting/standing) can beeasily compared. There is no described provision for the immediate andexact calculation of the relative orientation of the recorded vector inthe '850 patent.

In one embodiment, the present invention contemplates a methodcomprising calculating the relative spatial orientation of intracardiacEMG device leads to that of traditional sEKG electrodes (i.e., forexample, a 12-way electrode pattern). Although it is not necessary tounderstand the mechanism of an invention, it is believed thattransformation of implanted device intracardiac vector recordings toform reconstruction correlations of the surface electrocardiogram usesknowledge of the spatial orientation of the leads.

In one embodiment, the present invention contemplates a methodcomprising recording a simultaneous traditional sEKG with an implanteddevice EMG recording by calculating EMG/sEKG correlations. In oneembodiment, the calculating comprises developing a transformationalgorithm capable of recreating an orthogonal vectorcardiogram and/orreconstructed electrocardiogram. In one embodiment, the sEKG andintracardiac EMG recordings are made at the same time. In oneembodiment, the sEKG and intracardiac EMG recordings are made atdifferent times. Although it is not necessary to understand themechanism of an invention, it is believed that sEKGs recorded at adifferent time from an intracardiac EMG recording, the patient EKGshould be substantially similar during both recordings.

In one embodiment, the present invention contemplates a methodcomprising reconstructing an rEKG using EMG/sEKG correlations andintracardiac EMG vectors. Although it is not necessary to understand themechanism of an invention, it is believed that once EMG/rEKGcorrelations are obtained in a subject, a subsequent rEKG does notrequire a paired sEKG for comparison. In one embodiment, the methodfurther comprises avoiding electrical interference from near field EMGsby placing the implanted device and/or leads sufficiently far from themyocardium. In another embodiment, the method further comprises avoidingelectrical interference from near field EMGs by recording from a leadduring periods in cardiac cycle without adjacent myocardialdepolarization.

V. Method For 12-Lead Reconstruction

In one embodiment, correlation transformations relating the intracardiacand surface/external recordings are formed according to segmentaltemporal indexing to the QRST depolarization pattern. In one embodiment,each portion of the cardiac depolarization cycle has its own relationbetween the device and surface recordings. In one embodiment, therelationship may be direct matrix transformation or include scaling,filtering, or other post-processing as needed to ensure fidelity. In oneembodiment, the transformation may change based on empiric relationshipas the recorded depolarization pattern changes. In one embodiment,during each segment, different or redundant device recording leadvectors may be emphasized or removed by aspects of the transformation.

In one embodiment, multiple dipoles are used as a model to generate therelationship between intracardiac and surface/external recordings. Inone embodiment, these multiple dipole locations are empiricallydetermined and located in a configuration in three-dimensional space tomaximize fidelity between the correlated tracings. In one embodiment,the dipoles are assigned weighting based on their proximity to therecording lead and the temporal location of the cardiac depolarizationwavefront. In one embodiment, this relationship may include temporaryaugmentation of the effect of a nearby dipole, or the removal of thisdipole during a blanking period due to nonlinear, near-field, or otherundesirable effects.

In one embodiment, complete three-dimensional models of cardiacdepolarization are formed through voltage mapping from imaging or bodysurface potential mapping, with potential supplementation from externalone-time imaging modalities including MRI or CT, and used to model thedepolarization pattern and thus compute a relationship between theintracardiac device potentials and the surface EKG.

VI. Methods for Using rEKGs

In one embodiment, the present invention contemplates utilizing existingdata obtained from intracardiac EMG's to generate an rEKG in real-timeand continuously, for the purposes of monitoring, diagnosing, andtreating patients.

Currently, there are no implantable devices being used to detectischemia, myocardial infarction, electrolyte imbalances, or drug effectson the heart (i.e., for example, QT prolongation). Current technologyhas only provided implanted devices that detect EMG's for heart rhythmdiscrimination.

In one embodiment, the present invention contemplates a method fordiagnosing and/or treating a patient for conditions selected from thegroup comprising ischemia, myocardial infarction, cardiac toxicity frommedications, electrolyte imbalances, etc. In one embodiment, an rEKG canbe used to discriminate between various forms of abnormal rhythms ofboth ventricular and supraventricular origins. In one embodiment, anrEKG can be used for warning the patient about an abnormality. Thisresults in the utility of seeking early medical attention as well asinitiating automated intervention by an implanted device (i.e., forexample, delivery of medication or early warning to a 911-emergencyfrequency or other a remote medical monitoring station).

In one embodiment, the present invention contemplates a method forreconstructing an individualized 12-lead surface EKG through vectortransformation from intracardiac EMG's. In one embodiment, a patient mayhave a 3-vector intracardiac EMG recorded. In one embodiment, a firstvector is recorded from an implanted device to an RV distal tip. In oneembodiment, a second vector is recorded from an implanted device to aproximal coil on an RV lead. In one embodiment, a third vector isrecorded from a region selected from the group comprising the implanteddevice, distal coil, or proximal coil to a tip of a right atrial leadand/or left ventricular lead, or any other intrathoracic electrodesystem (i.e., for example, a subcutaneous array, epicardial patches orleads). In one embodiment, the method further comprises simultaneouslyrecording a 12-lead surface EKG.

In one embodiment, the method further comprises transforming therecorded EMGs and sEKGs into a EMG/sEKG correlation parameter. Althoughit is not necessary to understand the mechanism of an invention, it isbelieved that this transformation will encompass information about leadelectrodes and implanted device positions as well as about chestgeometry and heart positioning within the chest. It is further believedthat because the heart shifts within the chest in response to differentbody positions, a different transformation, and therefore a differentEMG/sEKG correlation parameter, can be obtained for these multiplepositions including, but not limited to, the supine, prone, standing,sitting, and decubitus positions.

In one embodiment, the method further comprises using the EMG/sEKGcorrelation parameter to generate an rEKG while continuously processingEMG in real time. In one embodiment, the EMG/sEKG correlation parameteris automatically changed upon receiving altered input from a positionalsensor within the implanted device. In one embodiment, the altered inputchanges the EMG/sEKG correlation parameter from supine to prone. In oneembodiment, the altered input changes the EMG/sEKG correlation parameterfrom standing to sitting. In one embodiment, the altered input changesthe EMG/sEKG correlation parameter from sitting to decubitus.

In one embodiment, the method further comprises analyzing the rEKG inreal time within the implanted device and/or a remote telemetry station.In one embodiment, the analyzing identifies an rEKG thresholdexceedance. In one embodiment, the rEKG threshold exceedance identifiesa condition including, but not limited to, ischemia, myocardialinfarction, drug toxicity, and/or electrolyte imbalances. In oneembodiment, the method further comprises alerting either the subjectand/or medical personnel to take appropriate actions in response to anrEKG threshold exceedance.

VII. Calculation of an rEKG

Various mathematical techniques could be applied to reconstruct a12-lead surface EKG from 3 independent intracardiac (IC) EMG vectors.For example, by using an IC EMG and the spatial position of the variousintracardiac electrodes as determined by imaging, such as, but notlimited to a CT scan or an MRI. Alternatively, by using an IC EMG and abaseline 12-lead EKG obtained simultaneously. The method describedherein is only one of a multitude of possible methods. The extent ofthis invention disclosure is not limited to this method but encompassesall other possible methods of reconstruction of 12-lead surface EKG fromIC EMGs.

A “device axes” refers to the orientation in 3-space of the basisvectors for measurement of electrical readings of the implanted device.EKG axes refer to the orientation of the vectors to which the standardcardiac electrical activity are projected (e.g. I, II, III, VI, etc.)

An arbitrary vector V on lead I may be expressed by:i=V·I=Σ(dim)v(i)I(i)  (1)For any vector of dimension n, v(n), a complete set of basis vectors isdefined by n non-collinear vectors. Thus, for n=3 (3d space), vectorv=[v(x) v(y) v(z)] on the basis vectors:A=[a(x)a(y)a(z)],B=[b(x)b(y)b(z)],C=[c(x)c(y)c(z)],wherea=a(x)v(x)+a(y)v(y)+a(z)v(z)b=b(x)v(x)+b(y)v(y)+b(z)v(z)c=c(x)v(x)+c(y)v(y)+c(z)v(z)and,[abc]=[A|B|C]·[v(x)v(y)v(z)],  (2)and[v(x)v(y)v(z)]=[A|B|C] ⁻¹ [abc].  (3)If one starts with an “encoded” vector v on basis i, j, and k, similarlyv=[v(x) v(y) v(z)] andi=[i(x)i(y)i(z)]j=[j(x)j(y)j(z)]k=[k(x)k(y)k(z)]and measured projection [i j k] on basis vectors i, j, and k, need [a bc] on basis vectors a, b, and c.

Consequently, we have:v=[I|J|K] ⁻¹(ijk)  (4)and(abc)=[A|B|C]·v  (5)thus,(abc)=[A|B|C]·[I|J|K] ⁻·(ijk)  (6)This result is similar to change of basis operations as used in linearalgebra.

In one embodiment, reconstruction of a known basis vector orientation ofvectors A, B, and C, an arbitrary vector can be projected onto new basisusing (1). In one embodiment, standard 12-lead sEKG data may bereconstructed from EKG measurement of any three non-planar vectors ofknown orientation through (1).

In one embodiment, the present invention contemplates the reconstructionof unknown basis vectors. Although it is not necessary to understand themechanism of an invention, it is believed that by using multiplereadings of the same electrical activity vector in three-dimensionalspace, it is possible to solve for an unknown basis vector set in termsof known basis vectors.

An “unknown basis set” as used herein, refers to measurements from animplanted device. A “known basis set” as used herein, refers theorientation of lead positions on a standard electrocardiogram (i.e., forexample, an sEKG).

In one embodiment, the present invention contemplates solving threeunknown basis vectors by using a minimum of three simultaneousmeasurements of known-axis projections of a given vector. In oneembodiment, the solving comprises an exact solution. In one embodiment,a standard depolarization loop (a single or signal-averaged QRS complex)is simultaneously recorded in both the surface and device projectionaxes, thereby providing a plurality of discrete measurement points. Inone embodiment, the discrete measurement points are used to calculatethe EMG/sEKG correlation parameter.

Although at least one of the above embodiments provides an exactsolution for three unknown basis vectors, exhaustive search approachesmay also be used to find unknown implanted device axes. In oneembodiment, basis vectors for the implanted device are proposed and aprojection of a known ventricular cardiogram (VCG) and/or recorded sEKGtracing onto this proposed basis is calculated. The method furthercomprises comparing the calculated basis vector projection to recordedmeasurements from an implanted device, thereby providing a score basedon scaled differences. The method further comprises repeating thisprojection and scaled score calculation for all possible basis vectors,with the best scoring vector (i.e., for example, the closest fit) ischosen as the basis vector for the implanted device.

In alternative embodiment, the exhaustive search method comprisesiterative refinement, wherein the proposed basis vectors arecontinuously compared to the expected output and altered in a directionto improve the correlation. Although it is not necessary to understandthe mechanism of an invention, it is believed that this modificationprovides for faster search times and ultimately increased precision.

Once the calculated EMG/sEKG correlation determines the relative axes ofmeasurement (basis vectors) for the implanted device, the method furthercomprises directly calculating an rEKG using EMG input and the EMG/sEKGcorrelation. Alternative embodiments comprise providing an intermediateconversion of the EMG input into a vectorcardiogram and subsequentprojection into known standard EKG recording leads.

VIII. Cardiac Diseases

The present invention contemplates several embodiments wherein cardiacdiseases are either detected and/or treated by real-time rEKGmonitoring. One advantage of the present invention is that a patienthaving an implanted cardiac device capable of transmitting EMGinformation can be continuously monitored for cardiac function.

While several illustrative cardiac diseases detected by some embodimentsof the present invention are discussed below, other diseases may bedetected by these embodiments as well. In one embodiment, the methoddetects cardiac structural diseases, including but not limited to,cardiac muscle diseases (i.e., for example, pericarditis, myocarditis,etc.). In one embodiment, the method detects pulmonary diseases (i.e.,for example, pulmonary embolism, pulmonary hypertension, chronicobstructive pulmonary disease, etc.). In one embodiment, the methoddetects central nervous system disorders (i.e., for example, stroke,cranial bleeding, etc.). In one embodiment, the method detects cardiacconduction system diseases (i.e., for example, sick sinus syndrome,atrioventricular nodal block of degrees 1, 2 and 3, etc.). In oneembodiment, the method detects respiratory rate via small variations inimpedance. In one embodiment, such impedance measurements could be usedto enhance the specificity of a diagnosis, and to compensate/reproducethe changes in the EKG-device relationship caused byrespiratory-dependent changes in heart position.

A. Ischemic Cardiomyopathy

Ischemic cardiomyopathy is generally believed to lead to congestiveheart failure due to coronary artery disease. Patients with thiscondition may at one time have had a heart attack, angina, or unstableangina. A few patients may not have noticed any previous symptoms. Asused herein the term “ischemic” means that an organ (such as the heart)is not getting enough blood and oxygen. Ischemic cardiomyopathy resultswhen the arteries that bring blood and oxygen to the heart are blocked.There may be a build-up of cholesterol and other substances, calledplaque, in the arteries that bring oxygen to heart muscle tissue.Ischemic cardiomyopathy is the most common type of cardiomyopathy in theUnited States and affects approximately 1 out of 100 people, most oftenmiddle-aged to elderly men.

Risk factors for ischemic cardiomyopathy include, but are not limitedto, personal or family history of heart attack, angina, unstable angina,atherosclerosis, or other coronary artery diseases; high blood pressure;smoking; diabetes; high fat diet; high cholesterol; and/or obesity.

Symptoms of ischemic cardiomyopathy include, but are not limited to,chest pain; palpitations; irregular or rapid pulse; shortness of breath;cough; fatigue, weakness, faintness; decreased alertness orconcentration; decreased urine output; excessive urination at night;overall swelling; and/or breathing difficulty when lying down. Aphysical examination may be normal, or it may reveal signs of fluidbuildup (leg swelling, enlarged liver, “crackles” in the lungs, extraheart sounds, or an elevated pressure in the neck vein). There may beother signs of heart failure. A diagnosis of ischemic cardiomyopathy iscurrently limited to a test showing that the pumping function of theheart is too low (i.e., for example, decreased ejection fraction). Anormal ejection fraction is around 55-65%, but most ischemiccardiomyopathy patients have a much lower ejection fraction.

Several types of medications have been prescribed for ischemiccardiomyopathy including, but not limited to, angiotensin convertingenzyme inhibitors (i.e., for example, captopril or lisinopril),adrenergic beta-blockers (i.e., for example, metoprolol or carvedilol),and diuretics (i.e., for example, furosemide, spironolactone, oreplerenone).

B. Angina Pectoris

Angina pectoris is referred to as a stable angina having chest pain ordiscomfort that typically occurs with activity or stress. The painusually begins slowly and gets worse over the next few minutes beforegoing away. It quickly goes away with medication or rest, but may happenagain with additional activity or stress. Angina is caused by too littleblood flow to the heart. The most common cause of angina is coronaryheart disease (CHD). Situations that increase blood flow to the heartmay cause angina in people with CHD. These include exercise, heavymeals, and stress.

Some risk factors for angina include, but are not limited to, maleness;diabetes; family history of coronary heart disease before age 50; highblood pressure; high LDL cholesterol and low HDL cholesterol; lack ofexercise; obesity; and or smoking. The most predominant symptom forangina comprises chest pain that occurs behind the breastbone orslightly to the left and feels like a tightness, heavy pressure,squeezing, or crushing pain. The pain may spread to shoulder, arm, jaw,neck, back, or other areas. The pain typically occurs after activity,stress, or exertion and lasts 1 to 15 minutes and can be relieved withrest and/or nitroglycerin administration. Other medicines that may beused to treat angina include, but are not limited to, blood thinners(i.e., for example, coumadin, aspirin or clopidogrel);cholesterol-lowering drugs; and blood pressure medicines (i.e., forexample, calcium channel blockers, beta blockers, andangiotensin-converting enzyme (ACE) inhibitors).

C. Myocardial Infarction

A myocardial infarction is the medical term for the more commonly usedterm, heart attack, and is a consequence of low blood flow causing theheart to starve for oxygen. Heart muscle dies or becomes permanentlydamaged. Most heart attacks are caused by a blood clot that blocks oneof the coronary arteries. The coronary arteries bring blood and oxygento the heart. If the blood flow is blocked, the heart starves for oxygenand heart cells die. A clot most often forms in a coronary artery thathas become narrow because of the build-up of a substance called plaquealong the artery walls. Sometimes, the plaque cracks and triggers ablood clot to form. Occasionally, sudden overwhelming stress can triggera heart attack.

Some estimates suggest that as many as 200,000 to 300,000 people in theUnited States die each year before medical help is sought, therebyartificially lowering the actual diagnosis rate. It is estimated,however, that approximately 1 million patients visit the hospital eachyear with a heart attack. About 1 out of every 5 deaths are due to aheart attack.

Risk factors for a myocardial infarction include, but are not limitedto, hereditary factors; maleness; diabetes; aging; high blood pressure;smoking; high fat diet; high LDLs and low HDL (“good”) cholesterol.Alternatively, higher-than-normal levels of homocysteine, C-reactiveprotein, and fibrinogen may also increase myocardial infarction risk.

While chest pain is the predominant symptom of a myocardial infarction,sometimes little or no chest pain occurs (i.e., for example, a silentheart attack). The pain may be felt in only one part of the body or movefrom your chest to your arms, shoulder, neck, teeth, jaw, belly area, orback. The pain can be severe or mild and feel like a squeezing or heavypressure; a tight band around the chest; heavy chest; and/or badindigestion. The Pain usually lasts longer than 20 minutes and, unlikeangina pectoris, rest and nitroglycerin does not completely relieve thepain. Other symptoms of a heart attack include but are not limited to,shortness of breath; nausea or vomiting; anxiety; cough; fainting;lightheadedness; dizziness; palpitations; and/or sweating.

D. Electrolyte Abnormalities

Electrolytes are minerals in your blood and other body fluids that carryan electric charge. It is important for the balance of electrolytes inyour body to be maintained, because they affect the amount of water inyour body, blood pH, muscle action, and other important processes. Youlose electrolytes when you sweat, and these must be replenished bydrinking lots of fluids.

Electrolytes exist in the blood as acids, bases, and salts (such assodium, calcium, potassium, chlorine, magnesium, and bicarbonate) andcan be measured by laboratory studies of the blood serum.

Any increased and/or decreased level of blood serum electrolyte alterthe ability of a cell membrane (i.e., for example, a cardiac cellmembrane) to properly maintain its electrical potential. In the case ofa cardiac cell membrane an altered electrical potential has an adverseeffect on the ability to depolarize and maintain a synchronized heartbeat. Such a condition can lead to heart rhythm abnormalities such areventricular tachycardia, supraventricular tachycardia, atrialarrhythmias, and/or ventricular arrhythmias.

E. Cardiac Arrhythmias

A cardiac arrhythmia is generally considered any disorder of the heartrate or heart rhythm, such as beating too fast (i.e., for example,tachycardia), too slow (i.e., for example, bradycardia), or beatingirregularly.

Normally, a 4 chambered heart (i.e., for example, 2 atria and 2ventricles) contract in a very specific, coordinated manner. Theelectrical impulse that signals a heart to contract in a synchronizedmanner begins in the sinoatrial node (SA node), which is a group ofcells that regularly, and spontaneously, depolarize thereby acting as anatural pacemaker. The depolarization signal leaves the SA node andtravels through the 2 upper chambers (atria). Then the depolarizationsignal passes through another node (the AV node), and finally, throughthe lower chambers (ventricles). This path enables the chambers tocontract in a coordinated fashion.

Problems can occur anywhere along this conduction system, causingvarious arrhythmias. Examples include, but are not limited to: i)supraventricular tachycardia: a fast heart rate that originates in theupper chambers (atria), wherein the most common are atrial fibrillationor flutter, and atrioventricular nodal reentry tachycardia; ii)ventricular tachycardia: a fast heart rate that originates in the lowerchambers (ventricles); and iii) bradycardia: a slow heart rate due toproblems with the SA node's pacemaker ability, or other interruption inconduction through the natural electrical pathways of the heart.

The risks of getting a tachycardia or bradycardia varies greatly,depending on the condition of your heart, prior heart attack, bloodchemistry imbalances, or endocrine abnormalities.

Arrhythmias may also be caused by some substances or drugs, including,but not limited to, adrenergic beta blockers, psychotropics,sympathomimetics, caffeine, amphetamines, or cocaine. Sometimesantiarrhythmic medications—prescribed to treat one type ofarrhythmia—can actually cause another type of arrhythmia. Some types ofarrhythmias may be life-threatening if not promptly and properlytreated.

Symptoms of arrhythmias may include, but are not limited to, fast orslow heart beat, palpitations; skipping beats; fainting;light-headedness; dizziness; chest pain; shortness of breath; changes inpulse pattern; paleness; sweating; and/or cardiac arrest

Current treatment to restore a normal rhythm may include, but are notlimited to, intravenous medications, electrical “shock” therapy (i.e.,for example, defibrillation or cardioversion), or implanting a temporarypacemaker to interrupt the arrhythmia.

Supraventricular arrhythmias may be treated with anti-arrhythmic drugs.However, some supraventricular arrhythmias can be treated and cured withradiofrequency ablation, eliminating the need for lifelong drug therapy.

Increasingly, most ventricular tachycardias are treated with animplantable cardioverter-defibrillator (ICD). As soon as arrhythmiabegins, the ICD sends a shock to terminate it, or a burst of pacingactivity to override it.

Bradycardias that cause symptoms can be treated by implanting apermanent pacemaker.

Experimental

I. Animal Studies

Preliminary experimental results using EKG reconstruction in pigssuggest that ischemia detection and localization occur in the majorcoronary artery distributions. Further, such data reflects the variouseffects of medications such as procainamide, isuprel, and others usingthe ventricular EMG vectors obtained from implanted devices (data notshown).

Animal studies have been completed using pigs showing that 12-lead EKGwere reconstructed in an individualized way from intracardiac EMG's andthat the resulting rEKG's can detect ischemia in the differentterritories of the coronary vasculature (the left anterior descendingartery, the Left circumflex artery, and the right coronary artery). Inthese studies, an implantable defibrillator was surgically placed inpigs followed by cardiac catheterizations. During the catheterizations,the coronary arteries were temporarily occluded intracardiac signalsdetected by the defibrillator were recorded. 12-lead sEKG's were alsorecorded at baseline and during coronary occlusion. rEKG's were thencalculated using the sEKG and EMG data that were similar to the recordedones and reliably identified ischemia.

The data provides paired comparisons of rEKG tracings to thecorresponding sEKG tracings for electrode leads I, III, & V1. See, FIGS.3-5 respectively.

II. Human Patients

The method of reconstruction of a 12-lead EKG from intracardiacrecordings by using multiple matrices, as opposed to only one matrix,has been examined in human patients with an implanted defibrillator. Theconcept of reconstructing a 12 lead EKG from the intracardiac signalrecorded from the ICD involves finding a transformation that would takeus from one to the other. The transformation is a matrix of numbers. Thetransformation can be made simple (1 matrix to convert from IC signal tosurface EKG) or complex (multiple matrices). In a multiple matrixtransformation, the cardiac cycle (1 beat with a P wave, a QRS wave, anda T wave) is divided into multiple portions, with each portion beingrepresented by a separate matrix. The number of divisions can vary fromone to more than two thousand. While computational complexity increasesas the number of matrices increase, the result is a higher fidelity EKGreconstruction.

The graphs in FIGS. 6 and 7 depict the superimposed tracings of recorded(blue) and reconstructed (red) EKG tracings obtained from three EKGprojections (AvR, AvL and AvF) in human patients with an implanteddefibrillator. The AvR, AvL and AvF projections represent three (3) outof the standard twelve (12) projections of the 12-lead EKG.

The reconstructed EKG projections depicted in FIG. 6 represent 700matrix relationships. Note that the major deflections are largelypreserved as compared to the recorded (original) EKG tracings. FIG. 6also demonstrates that in Lead AvR, the T wave of the third beat has analtered morphology.

The reconstructed EKG projections depicted in FIG. 7 represent 100matrix correlations. As demonstrated by FIG. 7, areas of poorcorrelation have a more significant effect.

What is claimed is:
 1. A method, comprising: a) providing: i) a subjectexhibiting symptoms of a cardiac disease, wherein said subject has animplanted cardiac device; ii) a system comprising said implanted cardiacdevice and a microprocessor wherein said microprocessor comprises aplurality of reconstructed electrocardiogram (rEKG) thresholdexceedances, wherein said microprocessor is capable of calculating asubject specific rEKG; iii) a testing parameter known to detect saidcardiac disease; b) calculating said subject specific rEKG with saidmicroprocessor while said testing parameter is administered to saidsubject; and c) comparing said subject specific rEKG to said pluralityof rEKG threshold exceedances with said microprocessor by analyzing ordisplaying said subject-specific rEKG such that said cardiac disease isdiagnosed, and d) signaling a warning with said implanted cardiac deviceabout said diagnosed cardiac disease.
 2. The method of claim 1, whereinsaid diagnosed cardiac disease comprises ischemia.
 3. The method ofclaim 1, wherein said diagnosed cardiac disease comprises electrolyteabnormalities.
 4. The method of claim 1, wherein said diagnosed cardiacdisease comprises a myocardial infarction.
 5. The method of claim 1,wherein said analyzing said rEKG comprises heart rhythm discrimination.6. The method of claim 1, wherein said testing parameter comprises atleast one medication.
 7. The method of claim 1, wherein said testingparameter comprises a stress test.
 8. The method of claim 1, whereinsaid testing parameter comprises a salt complex.
 9. The method of claim1, wherein said warning is in response to at least one of said pluralityof threshold exceedances.
 10. The method of claim 1, wherein saidwarning establishes said diagnosis of said cardiac disease.
 11. Themethod of claim 1, wherein said warning is in regards to delivery of amedication.
 12. The method of claim 1, wherein said warning istransmitted to a remote medical monitoring station.
 13. The method ofclaim 1, wherein said warning is transmitted to an emergency frequency.14. The method of claim 13, wherein said emergency frequency is atelephone 911 emergency frequency.